A 3′-protected route toward the synthesis of diastereomers clinically active ProTides, NUC-1031 and NUC-3373, is described. The in vitro cytotoxic activities individual were found to be similar their diastereomeric mixtures. In KG1a cell line, NUC-3373 have preferential effects on leukemic stem cells (LSCs). These not diastereomer-specific observed with parental nucleoside analogues gemcitabine...

Internal tandem duplication mutations of the FLT3 gene (FLT3/ITD mutations) are the most frequent molecular abnormality in acute myeloid leukemia (AML) and are associated with a poor overall survival. While the normal FLT3 receptor is expressed in early hematopoietic progenitor cells, it has not been determined whether FLT3 mutations are present in the leukemic stem cells. In this study, we sor...

Chronic Myeloid Leukemia (CML) is effectively treated with Tyrosine Kinase Inhibitors (TKI) such as Imatinib Mesylate (IM) targeted against BCR-ABL, however, several mathematical models and ex vivo-examinations suggested that IM does not eradicate CML stem cells. We previously reported the investigation of residual CML diseases during TKI treatment using FACS-sorting and quantitative RT-PCR of ...

Spleen colony assays were used to quantitate the cytocidal effect of actinomycin D on leukemic cells and normal hematopoietic stem cells. Different doses of actinomycin D were administered to either normal or leukemia-bearing mice, and the surviving fraction of these cell populations was determined. Following single injections of the drug, the killing of both the normal and leukemic cell popula...

Maintaining stemness of leukemic stem cells (LSCs) and reciprocal interactions between leukemia and stromal cells support leukemic progression and resistance to chemotherapy. Targeting the niche-based microenvironment is thus a new approach for leukemia therapy. Cordycepin is an analogue of adenosine and has been suggested to possess anti-leukemia properties. However, whether cordycepin influen...

BACKGROUND Lnk plays a non-redundant role by negatively regulating cytokine signaling of TPO, SCF or EPO. Retroviral expression of Lnk has been shown to suppress hematopoietic leukemic cell proliferation indicating its therapeutic value in cancer therapy. However, retroviral gene delivery carries risks of insertional mutagenesis. To circumvent this undesired consequence, we fused a cell permeab...